The broad goal of this research plan is to achieve a better understanding of the biochemical and molecular pathogenesis of the common degenerative disorder of the nervous system in the elderly which is Alzheimer's disease. The etiologic clues for this disease remain unknown. In this project we seek to uncover such clues by pursuing two closely related objectives. Our first priority will be a biochemical characterization and comparison of the abnormal neuronal fibrous proteins to their counterpart in normal tissue. The abnormal fibrous structures are the pathological hallmark of human dementia. The available method for the isolation of the abnormal fibrous structures appears to be inadequate. Various reagents will be tested to improve the yield and purity of the protein(s). Secondly, the pathologically occurring protein(s) will be compared by immunohistologcal approach with analogous proteins which are found to accumulate in the brains of apparently normal aged individuals.